COVID-19 Image Segmentation Algorithms Based on Conditional Generative Adversarial Network

The size and location of the lesions in CT images of novel corona virus pneumonia (COVID-19) change all the time, and the lesion areas have low contrast and blurred boundaries, resulting in difficult segmentation. To solve this problem, a COVID-19 image segmentation algorithm based on conditional generative adversarial network (CGAN) is proposed. Uses the improved DeeplabV3+ network as a generator, which enhances the extraction of multi-scale contextual features, reduces the number of network parameters and improves the training speed. A Markov discriminator with 6 fully convolutional layers is proposed instead of a common discriminator, with the aim of focusing more on the local features of the CT image. By continuously adversarial training between the generator and the discriminator, the network weights are optimised so that the final segmented image generated by the generator is infinitely close to the ground truth. On the COVID-19 CT public dataset, the area under the curve of ROC, F1-Score and dice similarity coefficient achieved 96.64%, 84.15% and 86.14% respectively. The experimental results show that the proposed algorithm is accurate and robust, and it has the possibility of becoming a safe, inexpensive, and time-saving medical assistant tool in clinical diagnosis, which provides a reference for computer-aided diagnosis. © 2022 ACM.

Role of toll-like receptors in the pathogenesis of COVID-19: Current and future perspectives

The coronavirus disease 2019 (COVID-19) pandemic underlines a persistent threat of respiratory tract infectious diseases and warrants preparedness for a rapid response. At present, COVID-19 has had a serious social impact and imposed a heavy global burden on public health. The exact pathogenesis of COVID-19 has not been fully elucidated. Since the outbreak of COVID-19, a renewed attention has been brought to Toll-like receptors (TLRs). Available data and new findings have demonstrated that the interaction of human TLRs and SARS-CoV-2 is a vital mediator of COVID-19 immunopathogenesis. TLRs such as TLR2, 4, 7 and 8 are potentially important in viral combat and activation of immunity in patients with COVID-19. Therapeutics targeting TLRs are currently considered promising options against the pandemic. A number of TLR-targeting immunotherapeutics are now being investigated in preclinical studies and different phases of clinical trials. In addition, innovative vaccines based on TLRs under development could be a promising approach for building a new generation of vaccines to solve the current challenges. In this review, we summarize recent progress in the role of TLRs in COVID-19, focusing the new candidate drugs targeting TLRs, the current technology and potential paths forward for employing TLR agonists as vaccine adjuvants.Copyright © 2023 The Scandinavian Foundation for Immunology.

Guidance on the use of biologic agents in psoriatic patients during COVID-19 outbreak.

The COVID-19 outbreak may have some impact on the use of biologics in psoriatic patients because immunosuppressive effects of biologics may potentially alter the susceptibility of patients to the virus, deteriorate the condition of infected patients or even change the prognosis of infection. According to currently available recommendations from international psoriasis academic organizations and specialists, as well as specific situation in China, the authors provide some guidance on the use of biologics for psoriatic patients undergoing or planning to undergo treatment with biologics, those with low or high risk of infection, and for those with or without COVID-19 infection, so as to provide references for clinical practice.Copyright © 2020 by the Chinese Medical Association.

COVID-19 and bone health.

A few patients who have recovered from COVID-19 develop persistent or new symptoms that last for weeks or months; this is called "long COVID" or "post-COVID-19 syndrome." Over time, awareness of the short- and long-term consequences of COVID-19 has increased. The pulmonary consequences are now fairly well established, but little is known about the extrapulmonary system of COVID-19, particularly its effects on bones. Current evidence and reports indicate a direct relationship between SARS-CoV-2 infection and bone health, with SARS-CoV-2 having a significant negative effect on bone health. In this review, we analyzed the impact of SARS-CoV-2 infection on bone health and assessed the impact of COVID-19 on the diagnosis and treatment of osteoporosis.

Impact of COVID-19 on perception and preparedness among clinical year Malaysian undergraduate dental students - A cross-sectional study

Objectives: This study aimed to evaluate how quarantine affected final-year dental students' self-perceptions of preparation and assess how online training affected clinical students' education at SEGi University. Methods: Year 3 to 5 students (n=140) were asked to fill up an online questionnaire. The first part included the effects of online education experience between the academic years. The second section assessed the graduating class's self-perceived readiness in cognitive, communication and professional abilities. The Chi-square test was used to analyse the association between the groups regarding academic years, gender, and family income. Results: Year 3 students missed educational experiences during lockdown significantly more than years 4 and 5 (p<0.001). In addition, 86% of year 5 students (p< 0.001) felt that online assessment was not a suitable evaluation method compared to the other clinical years. About two-thirds of the 5th year dental students were unsure of their confidence in their skills before graduation. Around half of the final-year students said they were unsure about starting their practice following graduation. After graduation, 80% of respondents preferred to spend a year in residence with sufficient training. Conclusions: Although students' self-perceived preparation was generally positive, they expressed reservations about the independent practice after graduation. Copyright: © 2021 Rath A, et al. This is an open access article licensed under a Creative Commons Attribution Work 4.0 United States License.

Research on the Spatiotemporal Evolution of China's Intercity Network Structure from the Perspective of the Relationship between Listed Companies and Customers

The connection between enterprises is an important part of urban connection. Strengthening the analysis of urban functional network based on the connection between enterprises is of great significance to enrich the theoretical research of urban network. Based on the trade relationship data between listed companies and their top five customers from 2010 to 2020, this paper constructs China's urban network, and analyzes the spatio- temporal evolution characteristics of urban network based on the perspective of trade links between enterprises. The research shows that: ① From 2010 to 2020, the urban network scale shows the characteristics of first rising and then falling, and the overall network density is low, ranging from 0.014 to 0.018. The center of gravity of the network presents the trend of "S" - shaped spatial trajectory change and overall southward movement.This feature is consistent with the trend of China's economic center moving southward in recent years. The overall spatial structure of the network changes from coastal to "T" - shaped structure. This feature is consistent with the "T" strategy of China's land development. ② The network traffic is concentrated in a few node cities. The total amount of capital in and out of the top 20 cities accounts for 71.9% of the total capital flow. Beijing and Shanghai are the absolute core of the network. The provincial capitals or sub provincial cities such as Hangzhou, Wuhan, Shenzhen and Guangzhou assume the function of regional centers. Foshan, Qiqihar, Nantong and other manufacturing developed cities are important nodes. It indicates that trade links are more likely to occur in cities with high administrative levels or developed industries. ③ The Pearl River Delta has the highest network density, which is between 0.324 and 0.334. The Yangtze River Delta has the highest total trade flow, which is 78.35 billion yuan. Although the networking level of urban agglomeration in the middle reaches of the Yangtze River and Chengdu Chongqing urban agglomeration is relatively low, they have become an important force to promote the evolution of network structure. ④ The COVID-19 has had a significant impact on the trade flow and network structure of the overall network. The network associations have been further divided and reorganized. The Guangzhou Shenzhen associations have been significantly strengthened. It shows that Guangzhou and Shenzhen have a strong combination effect. The Shanghai associations have been significantly weakened. The research results have a certain reference value for promoting the construction of domestic big cycle and unified big market. © 2023 Journal of Geo-Information Science. All rights reserved.

Joint Decisions of Components Replacement and Spare Parts Ordering Considering Different Supplied Product Quality

In addition to equipment maintenance decisions, spare parts ordering decisions from different suppliers play a key role in reducing related costs (e.g., maintenance, inventory and ordering costs). Since suppliers may use different production technologies and materials, spare parts (or products) from different suppliers can be different in quality. Nevertheless, in recent studies, the quality of spare parts is rarely considered to incorporate both equipment maintenance and spare parts ordering. In this paper, we investigate the joint optimization of condition-based maintenance and spare parts provisioning policy under two suppliers with different product quality. We formulate a sequential-decision problem with a Markov decision process and consequently obtain an optimal maintenance and ordering policy by an exact value iteration algorithm. To improve computation efficiency, based on the principle of sequential optimization, we develop heuristic methods. Extensive numerical experiments are conducted to assess the overall performance of the developed heuristic methods. Compared to the optimal method, results showed that the average cost gap is about 2% and computation time is reduced by 94% on average under the proposed heuristic method. Note to Practitioners—This paper is motivated by the observation that automobile industries tried to integrate emergency suppliers from which spare parts have different quality into maintenance schedules to avoid stockout and reduce equipment failure during the Covid-19 pandemic. Specifically, the article focuses on balancing the trade-offs between condition-based maintenance and inventory management from two suppliers with different lead times and spare parts quality for multi-unit systems. On the one hand, effective maintenance scheduling relies on spare parts for replacement to ensure the stability of production. On the other hand, inventory management needs to select the supplier with appropriate lead time and product quality to reduce the ordering cost and avoid stockout based on the degradation states of equipment. The joint optimization of these two aspects serves to reduce the total maintenance and ordering cost. Nevertheless, most existing research aims to optimize them separately. In this paper, we formulate the joint decision problem considering the two aspects based on a Markov decision process. We obtain an optimal maintenance and ordering policy by an exact value iteration algorithm and present heuristics to improve the computation efficiency when the system contains multiple machines. Practitioners can implement the proposed methodology to make condition-based maintenance and inventory management when spare parts with different qualities are ordered from two suppliers. To balance cost and computational efficiency, it is suggested to implement the optimal policy by an exact value iteration algorithm when the number of machines is small in the system and use the heuristic methods when the number of machines is large (i.e., usually larger than 3). IEEE

Hotspot and progress of minimally invasive gastrointestinal surgery.

The unprecedented year 2020 has passed. Under the shadow of the COVID-19 epidemic, the global political, social and economic patterns have changed dramatically. Due to the rapid control of epidemic spread in China, medical system soon returned to normal. Minimally invasive gastrointestinal surgery represented by laparoscopy has completely returned to normal level. In view of prevention and control of the epidemic, international communication and transportation have been greatly affected. Many academic conferences have been cancelled or changed to be held online. The epidemic has greatly accelerated the popularization of online transmission of minimally invasive surgery. However, there are some differentiation and differences in disease spectrum, surgical technology, minimally invasive technology, surgical equipment and instruments at home and abroad. In view of this special situation in 2020, this paper reviews and prospects the new hot spots and new developments of minimally invasive gastrointestinal surgery in terms of surgical technology platform, surgical technology and concept.Copyright © 2021 Chinese Medical Association

Hotspot and progress of minimally invasive gastrointestinal surgery.

The unprecedented year 2020 has passed. Under the shadow of the COVID-19 epidemic, the global political, social and economic patterns have changed dramatically. Due to the rapid control of epidemic spread in China, medical system soon returned to normal. Minimally invasive gastrointestinal surgery represented by laparoscopy has completely returned to normal level. In view of prevention and control of the epidemic, international communication and transportation have been greatly affected. Many academic conferences have been cancelled or changed to be held online. The epidemic has greatly accelerated the popularization of online transmission of minimally invasive surgery. However, there are some differentiation and differences in disease spectrum, surgical technology, minimally invasive technology, surgical equipment and instruments at home and abroad. In view of this special situation in 2020, this paper reviews and prospects the new hot spots and new developments of minimally invasive gastrointestinal surgery in terms of surgical technology platform, surgical technology and concept.Copyright © 2021 Chinese Medical Association

Concept renovation: a new perspective of minimally invasive surgery. TT -:.

The development and innovation of laparoscopic vision platform has promoted the innovation of surgical concept and technology from laparotomy to minimally invasive surgery. From the initial use of reflector device with candlelight to observe the interior of the human body cavity, to the high-definition and ultra-high-definition laparoscopic vision system, from laparoscopic cholecystectomy, to the popularization and promotion of various laparoscopic surgery for malignant tumor, surgery has undergone great changes due to minimally invasive technology. In the new era, the application of three-dimensional and 4K laparoscope brings a new perspective to minimally invasive surgery, so as to promote the development of surgery in the direction of accurate anatomy and functional protection. In the future, stimulated by concept renovation in post-epidemic era of COVID-19, virtual reality technology and robotic surgery supported by the fifth generation wireless systems, as well as tele-surgery and distance training and teaching based on it, will become a new perspective for the development of minimally invasive surgery.Copyright © 2020 by the Chinese Medical Association.

Sourcing decisions with uncertain time-dependent supply from an unreliable supplier

Recently, an increasing number of companies have encountered random production disruptions due to the COVID-19 pandemic. In this study, we investigate a two-stage supply chain in which a retailer can order products from a low-price ("cheap”) unreliable supplier (who may be subject to an uncertain production disruption and partially deliver the order) and an "expensive” reliable supplier at Stage 1 and a more "expensive” backup supplier at Stage 2. If the disruption happens, only the products that were produced before the disruption time can be obtained from the unreliable supplier. It is found that in the case with imperfect demand information updating, the unreliable supplier is always used while the reliable supplier can be abandoned. The time-dependent supply property of the unreliable supplier reduces the retailer's willingness of adopting the dual sourcing strategy at Stage 1, compared with the scenario with all-or-nothing supply. Different from the case with imperfect demand information updating, either the reliable or unreliable supplier can be abandoned in the case with perfect demand information updating. We derive the optimal ordering decisions and the conditions where single sourcing or dual sourcing is adopted at Stage 1. We conduct numerical experiments motivated by the sourcing problem of 3M Company in the US during the COVID-19 and observe that the unreliable supplier is more preferable when the demand uncertainty before or after the emergency order is higher. Interestingly, the retailer tends to order more from the unreliable supplier when the production disruption probability is larger in some cases. © 2022 The Author(s)

Efficacy and Safety of Ixekizumab in Chinese Patients with Moderate-to-Severe Plaque Psoriasis: 60-Week Results from a Phase 3 Study

Objective: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is approved for treating moderate-to-severe psoriasis. This phase 3, multicenter, randomized, double-blind, placebo-controlled trial (NCT03364309;registered December 6, 2017) evaluated the safety and efficacy of ixekizumab in Chinese patients with moderate-to-severe psoriasis. Method(s): 438 patients were randomized 2:2:1 to 80 mg ixekizumab every 2 weeks (IXE Q2W, n = 176), 80 mg ixekizumab every 4 weeks (IXE Q4W, n = 174), or placebo (n = 88). Efficacy was assessed by evaluating the static Physician's Global Assessment score of 0 or 1 (sPGA [0,1]) and Psoriasis Area and Severity Index (PASI) 75/90/100 responses, and nonresponder imputation was used for handling missing data. The safety profile was evaluated by assessing treatment emergent adverse events (AEs) and serious AEs. Result(s): At week 12, the sPGA (0,1) response rates were 3.4%, 79.9%, and 86.4% in the placebo, IXE Q4W, and IXE Q2W groups, respectively. The PASI 75/90/100 response rates were 8.0%/2.3%/0.0%, 87.4%/75.9%/29.3%, and 93.8%/82.4%/33.0% in the placebo, IXE Q4W, and IXE Q2W groups, respectively. Ixekizumab led to rapid PASI 50 responses, as early as week 1, whereas PASI 75 and sPGA (0,1) responses were observed from week 2. sPGA (0,1) and sPGA (0) responses were maintained through week 60 in a higher proportion of patients receiving IXE Q4W vs. placebo. The safety profile was consistent with previous studies of ixekizumab in psoriasis. Conclusion(s): Ixekizumab showed a rapid onset of action and high efficacy that was maintained through 60 weeks and was well tolerated with no unexpected AEs, in Chinese patients with moderate-to-severe plaque psoriasis. Copyright © 2022 International Journal of Dermatology and Venereology. All right reserved.

Hemophagocytosis in a Severe COVID-19 Patient

The novel coronavirus (SARS-CoV-2) infection has become a heavy burden on global health. Although the coronavirus disease 2019 (COVID-19) may adversely affect multiple organs and systems of infected patients, to the best of our knowledge, there is little investigation of the SARS-CoV-2's impact on bone marrow. Our clinical and cytological findings in this case of severe COVID-19 infection provide novel insights into the pathogenesis of SARS-CoV-2 infection in the hematopoietic system. We recommend that physicians consider SARS-CoV-2 infection's effect on bone marrow in patients who are slow to recover and suggest that a better understanding of the bone marrow morphology in COVID-19-infected patients is needed. © 2022 Journal of Bone and Joint Surgery Inc.. All rights reserved.

Pathogens inactivation in nutrient recovery from urine: A review

Urine source separation, a kind of new sewage management concept, has made great progress in technology development and application in the past 30 years. However, understanding of the potential microbial risks in reuse of urine derived fertilizer products (UDFPs) in agriculture is still lacking. Outbreak of pandemic of Coronavirus Disease 2019 and more deadly disease caused by Monkeypox strongly sounds the alarm bell to the attention on pathogens in urine and their fate in UDFPs. Therefore, this study presented a comprehensive review on pathogens inactivation in nutrient recovery technologies. The review suggests that technologies using alkaline or heating treatment can effectively reduce pathogens in UDFPs. However, technologies with characteristics such as membrane rejection of nutrients or nutrient adsorption may even concentrate pathogens in their fertilizer products. Based on an overall assessment, connections of technologies and the pathogens inactivation in their UDFPs have been established. This would help to provide a perspective on development of urine treatment technology and management of microbial risks in reusing urine nutrients in agriculture.

RESEARCH ON THE WILLINGNESS OF USERS' PRIVACY CONCERNS TO USE EPIDEMIC PREVENTION TECHNOLOGY UNDER THE BACKGROUND OF THE NEW CORONAVIRUS EPIDEMIC

Nowadays, governments worldwide use artificial intelligence (AI), big data, cloud computing, and other technologies to control the spread of the epidemic. These measures significantly improve the efficiency of virus tracking. Nevertheless, such digital defences have also raised concerns about privacy leaks. Privacy concerns and use intention have been studied in several areas in the existing literature, but few have been explored in-depth based on epidemic prevention. Therefore, this paper focuses on the background of the novel coronavirus epidemic and constructs a structural equation model based on the theory of privacy concern and technology acceptance model. The research studies the influence of privacy concerns, perceived risk, and other factors on users’ willingness to use new technologies. Based on 132 samples, the results show that privacy concerns significantly impact perceived risk. Perceived trust has significant positive impacts on self-disclosure intention. This study discusses individual self-disclosure intention in the field of public security from multiple perspectives. The research results extend the relevant theories on adopting and using emerging technologies. This study provides ideas on how to alleviate residents' privacy concerns in practice and helps government departments to carry out better prevention work. © 2022 CURRAN-CONFERENCE. All rights reserved.

SARS-CoV-2-SPECIFIC T CELLS ASSOCIATED with LUNG DYSFUNCTION in LONG COVID-19

Background: After infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a significant number of individuals develop post-acute sequelae of COVID-19 (PASC) marked by prolonged symptoms, including persistent pulmonary dysfunction. An estimated 5-20% of those infected with SARS-CoV-2 will go on to develop PASC. T cells and inflammation contribute significantly to severe COVID-19 and similar chronic conditions;however, little is known about the role of persistent inflammation and SARS-CoV-2-specific immunity in PASC. The objective of this study is to compare inflammatory markers, frequencies of SARS-CoV-2-specific T cells, and pulmonary function in subjects who recovered from acute COVID infection (AC) and PASC. Methods: We collected blood samples from 35 individuals after recovery from SARS-CoV-2 infection and divided the cohort by symptom duration into AC or PASC. We measured T cell responses to SARS-CoV-2 surface proteins, assessed levels of inflammatory markers in the plasma and measured pulmonary function. The Mann-Whitney U test were utilized to examine differences between groups. Correlations were calculated using the nonparametric Spearman test. P values of <0.05 were considered statistically significant. Results: Compared to AC, subjects with PASC had significantly elevated plasma CRP and IL-6 and up to a hundred-fold increase in the frequency of IFN-γ-and TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells in blood. Importantly, the frequency of SARS-CoV-2-specific, TNF-α-producing CD4+ and CD8+ T cells in PASC positively correlated with plasma IL-6 and negatively correlated with measures of lung function, including FEV1, while increased frequencies of IFN-γ-producing T cells were associated with the duration of respiratory symptoms during the post-acute period. Conclusion: Significant immunological differences exist between subjects with PASC and AC that are associated with increased inflammation and pulmonary dysfunction, suggesting that persistent immunologic differences may drive ongoing symptoms in PASC. The persistence of SARS-CoV-2-specific T cells in PASC suggests the presence of persistent viral reservoirs as a possible mechanism behind PASC etiology.

Application of Nanotechnology for Virus Inactivation in Water: Implications for Transmission over line Blocking of the Novel Coronavirus SARS over line CoV over line 2

The novel coronavirus pneumonia epidemic (COVID over line 19) brings a serious threat to the development of human society and the health of human beings. Due to the stability of the severe acute respiratory syndrome coronavirus 2 ( SARS over line CoV over line 2) in urban sewage, which has become one of the virus pollution sources, it has been a focus how to eliminate the existing virus in water. SARS over line CoV over line 2 structurally consists of RNA chains and protein capsids, and thus can be inactivated via reactive oxygen species ( ROS) attack. Moreover, block of biochemical metabolism and destruction of virus structure are also effective inactivation methods for SARS over line CoV over line 2 inactivation. Nanomaterials exhibit surface and interface effects, specific microstructure and excellent physicochemical properties, implying their high application potential in SARS over line CoV over line 2 inactivation. In this study, we overall review application of nanotechnologies for SARS over line CoV over line 2 inactivation, including photocatalysis, heterogeneous catalytic oxidation, ion toxicity induced inactivation, and structural effects inactivation method. Furthermore, based on the structural composition, as well as survival and transmission characteristics of SARS over line CoV over line 2 in water environment, the application potential of various nanotechnologies for SARS over line CoV over line 2 inactivation are deeply discussed. This study can provide a theoretical basis and practical reference for the application of nanotechnology for the SARS over line CoV over line 2 inactivation and the secondary transmission interruption in water.

Vida Decision Support System: An International, Collaborative Project for COVID-19 Management with Integrated Modeling

The Vida Decision Support System (Vida) is an application of the Environment-Vulnerability-Decision-Technology (EVDT) integrated modeling framework specifically aimed at COVID-19 impact and response analysis. The development of Vida has been an international collaboration involving multidisciplinary teams of academics, government officials (including public health, economics, environmental, and demographic data collection officials), and others from six states: Angola, Brazil, Chile, Indonesia, Mexico, and the United States. These collaborators have been involved with the identification of decision support needs, the surfacing and creation of relevant data products, and the evaluation of prototypes, with the vision of creating an openly available online platform that integrates earth observation instruments (Landsat, VIIRs, Planet Lab's PlanetScope, NASA's Socioeconomic Data and Applications Center, etc.) with in-situ data sources (COVID-19 case data, local demographic data, policy histories, mobile device-based mobility indices, etc.). Vida both visualizes historical data of relevance to decision-makers and simulates possible future scenarios. The modeling techniques used include system dynamics for public health, EO-based change detection and machine learning for environmental analysis, and discrete-event simulation of policy changes and impacts. In addition to the direct object of this collaboration (the development of Vida), collaborators have also benefited from sharing individual COVID-19-related insights with the network and from considering COVID-19 response in a more integrated fashion. This work outlines the Vida Decision Support System concept and the EVDT framework on which it is based. The international team is using Vida to evaluate the outcomes in several large cities regarding COVID cases, environmental changes, economic changes and policy decisions. It provides an overview of the overlapping and diverging needs and data sources of each of the collaborating teams, as well as how each of those teams have contributed to the development of Vida. The current state of the Vida prototypes and plans for future development will be presented. Additionally, this work will discuss the lessons learned from this development process and their relevance to other integrated applications. Copyright © 2021 by the International Astronautical Federation (IAF). All rights reserved.

Disease profile and plasma neutralizing activity of post-vaccination Omicron BA.1 infection in Tianjin, China: a retrospective study (preprint)

BackgroundSARS-CoV-2 Omicron variant BA.1 first emerged on the Chinese mainland in January 2022 in Tianjin and caused a large wave of infections. During mass PCR testing, a total of 430 cases infected with Omicron were recorded between January 8 and February 7, 2022, with no new infections detected for the following 16 days. Most patients had been vaccinated with SARS-CoV-2 inactivated vaccines. The disease profile associated with BA.1 infection, especially after vaccination with inactivated vaccines, is unclear. Whether BA.1 breakthrough infection after receiving inactivated vaccine could create a strong enough humoral immunity barrier against Omicron is not yet investigated. MethodsWe collected the clinical information and vaccination history of the 430 COVID-19 patients infected with Omicron BA.1. Re-positive cases and inflammation markers were monitored during the patients convalescence phase. Ordered multiclass logistic regression model was used to identify risk factors for COVID-19 disease severity. Authentic virus neutralization assays against SARS-CoV-2 wildtype, Beta and Omicron BA.1 were conducted to examine the plasma neutralizing titers induced after post-vaccination Omicron BA.1 infection, and were compared to a group of uninfected healthy individuals who were selected to have a matched vaccination profile. FindingsAmong the 430 patients, 316 (73.5%) were adults with a median age of 47 years, and 114 (26.5%) were under-age with a median age of 10 years. Female and male patients account for 55.6% and 44.4%, respectively. Most of the patients presented with mild (47.7%) to moderate diseases (50.2%), with only 2 severe cases (0.5%) and 7 (1.6%) asymptomatic infections. No death was recorded. 341 (79.3%) of the 430 patients received inactivated vaccines (54.3% BBIBP-CorV vs. 45.5% CoronaVac), 49 (11.4%) received adenovirus-vectored vaccines (Ad5-nCoV), 2 (0.5%) received recombinant protein subunit vaccines (ZF2001), and 38 (8.8%) received no vaccination. No vaccination is associated with a substantially higher ICU admission rate among Omicron BA.1 infected patients (2.0% for vaccinated patients vs. 23.7% for unvaccinated patients, P<0.001). Compared with adults, child patients presented with less severe illness (82.5% mild cases for children vs. 35.1% for adults, P<0.001), no ICU admission, fewer comorbidities (3.5% vs. 53.2%, P<0.001), and less chance of turning re-positive on nucleic acid tests (12.3% vs. 22.5%, P=0.019). For adult patients, compared with no prior vaccination, receiving 3 doses of inactivated vaccine was associated with significantly lower risk of severe disease (OR 0.227 [0.065-0.787], P=0.020), less ICU admission (OR 0.023 [0.002-0.214], P=0.001), lower re-positive rate on PCR (OR 0.240 [0.098-0.587], P=0.002), and shorter duration of hospitalization and recovery (OR 0.233 [0.091-0.596], P=0.002). At the beginning of the convalescence phase, patients who had received 3 doses of inactivated vaccine had substantially lower systemic immune-inflammation index (SII) and C-reactive protein than unvaccinated patients, while CD4+/CD8+ ratio, activated Treg cells and Th1/Th2 ratio were higher compared to their 2-dose counterparts, suggesting that receipt of 3 doses of inactivated vaccine could step up inflammation resolution after infection. Plasma neutralization titers against Omicron, Beta, and wildtype significantly increased after breakthrough infection with Omicron. Moderate symptoms were associated with higher plasma neutralization titers than mild symptoms. However, vaccination profiles prior to infection, whether 2 doses versus 3 doses or types of vaccines, had no significant effect on post-infection neutralization titer. Among recipients of 3 doses of CoronaVac, infection with Omicron BA.1 largely increased neutralization titers against Omicron BA.1 (8.7x), Beta (4.5x), and wildtype (2.2x), compared with uninfected healthy individuals who have a matched vaccination profile. InterpretationReceipt of 3-dose inactivated vaccines can substantially reduce the disease severity of Omicron BA.1 infection, with most vaccinated patients presenting with mild to moderate illness. Child patients present with less severe disease than adult patients after infection. Omicron BA.1 convalescents who had received inactivated vaccines showed significantly increased plasma neutralizing antibody titers against Omicron BA.1, Beta, and wildtype SARS-CoV-2 compared with vaccinated healthy individuals. FundingThis research is supported by Changping Laboratory (CPL-1233) and the Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3), sponsored by the Ministry of Science and Technology of the Peoples Republic of China. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrevious studies (many of which have not been peer-reviewed) have reported inconsistent findings regarding the effect of inactivated vaccines against the Omicron variant. On Mar 6, 2022, we searched PubMed with the query "(SARS-CoV-2) AND ((Neutralisation) OR (Neutralisation)) AND ((Omicron) OR (BA.1)) AND (inactivated vaccine)", without date or language restrictions. This search identified 18 articles, of which 13 were directly relevant. Notably, the participants in many of these studies have received only one or two doses of inactivated vaccine with heterologous booster vaccination; other studies have a limited number of participants receiving inactivated vaccines. Added value of this studyTo date, this is the first study to report on the protective effect of inactivated vaccines against the severe disease caused by the Omicron variant. We examine and compare the disease profile of adults and children. Furthermore, we estimate the effect of post-vaccination omicron infection on plasma neutralization titers against Omicron and other SARS-COV-2 variants. Specifically, the disease profile of Omicron convalescents who had received two-dose primary series of inactivated vaccines with or without a booster dose prior to infection is compared with unvaccinated patients. We also analyzed the effect of infection on neutralizing activity by comparing vaccinated convalescents with vaccinated healthy individuals with matched vaccination profiles. Implications of all the available evidenceCompared with adults, child patients infected with Omicron tend to present with less severe disease and are less likely to turn re-positive on nucleic acid tests. Receipt of two-dose primary series or three doses of inactivated vaccine is a protective factor against severe disease, ICU admission, re-positive PCR and longer hospitalization. The protection afforded by a booster dose is stronger than two-dose primary series alone. Besides vaccination, infection with Omicron is also a key factor for elevated neutralizing antibody titers, enabling cross-neutralization against Omicron, wildtype (WT) and the Beta variant.

Development of a Robust Manufacturing Route for Molnupiravir, an Antiviral for the Treatment of COVID-19

Herein is described the development of a large-scale manufacturing process for molnupiravir, an orally dosed antiviral that was recently demonstrated to be efficacious for the treatment of patients with COVID-19. The yield, robustness, and efficiency of each of the five steps were improved, ultimately culminating in a 1.6-fold improvement in overall yield and a dramatic increase in the overall throughput compared to the baseline process.